Noninvasive functional MRI with the blood oxygenation level-dependent contrast (fMRI-BOLD) method has been used with computationally principled temporal differential (TD) models to tease out neural valuation responses related to reward-learning and decision-making. A large and ever growing number of neuroimaging studies have examined brain responses to a variety of rewarding stimuli and valuations and suggested that the orbitofrontal cortex (OFC), ventral striatum, and ventral medial prefrontal cortex (vmPFC) form a Ventral Valuation Network. There is a gap in that no valuation studies with the drugs of abuse have been reported with human subjects. The question is: What mechanisms influence the dopaminergic system to assign a value of cocaine rewards to be used for action selection, i.e., decision-making? Our central hypothesis is that cocaine is a disease agent and that repeated cocaine use alters brain valuation circuitry in which the predictive error signal between the expected cocaine value and the outcome upon cocaine delivery goes awry; this could bias the decision-making processes and lead to addiction. We will use the fMRI- BOLD method with cocaine-dependent human subjects to test our hypothesis. Aim 1. Determine BOLD responses to three conditioned visual stimuli associated with three different cocaine doses in the MRI scanner environment before, during, and after the conditioned cocaine learning. Identify a set of neural structures especially in the Ventral Valuation Network that are related to cocaine expectancy and the predictive error signals between expectancies and cocaine-delivered outcome. Aim 2. Determine BOLD responses to the descending mismatches between the expected cocaine doses and the actual administered cocaine doses. Aim 3. determine BOLD responses to the ascending mismatches between the expected cocaine doses and the actual administered cocaine doses. The proposed study will greatly enhance our understanding of drugs of abuse and may potentially guide the development of new treatments for addiction. PUBLIC HEALTH RELEVANCE: It is hypothesized that cocaine is a disease agent and that repeated cocaine use alters brain valuation circuitry in which the predictive error signal between the expected cocaine value and the outcome upon cocaine delivery goes awry; this could bias the decision-making processes and lead to addiction. We will use the fMRI-BOLD method with cocaine-dependent human subjects to test our hypothesis. The proposed study will greatly enhance our understanding of drugs of abuse and may potentially guide the development of new treatments for addiction. [unreadable] [unreadable] [unreadable]